1. Field of the Invention
The present invention relates to a universal container for medicinal purposes and, more particularly, to a universal container for liquid and solid medicinal preparations.
This invention is particularly relevant to storage and in situ preparation of freeze-dried medicinal products. The problems occurring in this type of application are described in the following background section, but the invention is not limited to this particular application.
2. Prior Art
Special medicinal products, pharmaceuticals, such as diagnostic preparations, are marketed as freeze-dried products in containers, because of pharmaceutical lifetime and stability considerations. The freeze drying, the lyophilization, typically occurs in such a way that the liquid to be lyophilized in the container is subjected to a freeze-drying process, in which the container is washed prior to filling and is sterilized. After the freeze-drying closure with an elastic stopper occurs and the resulting product is conveyed to further processing steps. Immediately prior to use the lyophilized medicinal substance is dissolved by introducing a liquid and typically taken up in a syringe device with a needle.
A series of requirements or specifications have been established for the above-named container. The first requirements relate to the material used for the container.
Glass is given priority over plastic as the material used for the container for freeze-drying or for storage of the freeze-dried medicinal products. This is because glass provides an extraordinarily high barrier to water vapor or steam, CO2 and oxygen, in contrast to that provided by plastic and is thus universally useable for many medicinal products. Individual plastic materials have good barrier properties in relation to either water vapor or oxygen and carbon dioxide, but not however against water vapor or steam and oxygen/carbon dioxide to a sufficient extent for many ingredients to be contained in the container.
For special medicinal substances with minimal protection requirements and/or comparatively short storage times however, the container may be made of plastic material as the principal component. Up to now they are not widely used for parenteral preparations.
The glass containers for medicinal purposes currently on the market include tubular glass containers and blow-molded glass containers. The manufacturing methods for tubular glass containers and blow-molded glass containers are widely known. Tubular glass containers are made from pre-fabricated glass tubing by shaping and separation. Tubular glass containers include ampoules, bottles, cylindrical injector and syringe bodies, whose shape and size are standard. Blow-molded glass containers are made by shaping a glass melt directly by blowing or press-and-blow processes. The blow-molded glass containers include, for example, spray and infusion bottles, such as described in German Patent Document DE 196 22 550 A1 Glass containers for the above-named purposes also have the advantage in relation to plastic containers that they may be sterilized with known pharmaceutical methods, e.g. with heated air at temperatures of about 300xc2x0 C. This is especially true when the container is made from borosilicate glass, because borosilicate glass has a high thermal shock resistance, which is also significant for the lyophilization process with temperatures between xe2x88x9245xc2x0 C. and 30xc2x0 C.
The container should also be closable with standard closure methods and have a high stability. On the other hand, it is indispensable for freeze-drying in a container that the container be lightweight, since a minimal container mass (heat capacity) is desirable for the freeze-drying process, in order to be able to perform these expensive thermal processes as fast and as economically as possible.
It is important for the freeze-drying process (synonymous with lyophilization process) to attain as uniform as possible a crystal structure for the lyophilizate (synonymous with dried product) in order to guarantee a uniform and rapid dissolution by the user and to keep the edge effects as small as possible. Furthermore it is very important for the freeze-drying that breaking the container during the freeze-drying process is avoided. Both conditions must be maintained by using suitable container dimensions.
It has already been suggested to provide an additive, such as calcium chloride and lactose, in order to at least reduce bottle breakage. However this type of feature is only rarely acceptable, since the pharmaceutical composition of the product contained in the container must be changed in order to adjust it to an otherwise unsuitable container.
An additional problem with freeze-drying is collapse, namely that the formation of an amorphous frozen product, which is not converted into the crystalline state, occurs during freeze-drying. This effect must also be considered during the making of the glass container.
Another circumstance must be considered.
Freeze-dried medicinal products are very expensive because of their accompanying very expensive manufacturing technology. Thus it is important to be able to take the liquid contents of the container with a dissolved lyophilizate completely from the container as soon as possible. This is not possible with the conventional glass tubing or blow-molded glass containers or requires troublesome handling, e.g., shaking together of individual droplets and removal with a vacuum tube, an injector needle, etc. It is not practical to automate this process because the drop distribution is determined by chance, so that a complete removal of the liquid from the container in the case of an automatic removal method, e.g. by an automatic analysis unit, as takes place in analysis of blood, etc., is possible only to a very limited extent. This complete emptying of this type of container of course is generally very important, not only in the case of a freeze-dried product.
Furthermore the use of silicon oil for surface modification of freeze-dried containers, is prohibited, since this can lead to undesirable impurities in the lyophilizate after freeze-drying. Beyond this the use of silicone for parenteral products should only be used in absolutely exceptional cases, since injection of silicone droplets in the body should be absolutely prevented. This also is true not only for freeze-dried products, but also for all injection/infusion preparations in liquid or solid form.
Furthermore for reasons of rational processing and use of containers for liquids in general and not only for freeze-dried medicinal preparations, storage of different containers should be kept to a minimum.
The known bottles, which should be made from glass or plastic, however do not fulfill the above-described specifications completely.
It is an object of the present invention to provide a universal container for medicinal purposes, especially for freeze-dried products, of the above-described type which meets the above-described requirements.
It is another object of the present invention to provide a container for medicinal purposes of the above-described type that is very lightweight and still stable, that allows lyophilization, that leads to a homogeneous or uniform dried product, that has a reduced danger of breaking during the freeze-drying process and that permits an almost complete emptying of the liquid lypophilizate and is useable universally for liquid and solid medicinal preparations.
The container according to the invention comprises a casing section with a bottom portion and an outlet section. It has a thin-walled casing in comparison to its base, a molded outlet portion that is closable by a conventional closure and a geometrically nonuniform bottom portion that has at least one interior depression, a reinforced section and an outer bottom surface that is completely planar or planar with only a slight central indentation.
The structure of the container according to the invention provides a lightweight container with greater stability and guarantees a lyophilization process that produces a uniformly freeze-dried product. The container has only a very slight breakage rate and can be nearly completely emptied. Furthermore it is universally useable for liquids and solid filling materials.
Different features for the bottom portion of the container are possible in various different embodiments that are claimed in the appended dependent claims.
An ampoule made from plastic is known with a special configuration for the bottom portion, which is described in Japanese Abstract JP 08322908.
The contents of the ampoules are typically transferred into syringes in use. Also the outlet section of the known ampoule is formed so that a needle-less injector or syringe can be mounted on the ampoule. In order to transfer the contents of the ampoule, this xe2x80x9ctop-headxe2x80x9d must be empty so that the liquid contents can reach the syringe body. In order to make filling the injector or syringe easier, the bottom portion of the ampoule is conical with a central depression formed so that it is squeezed together. The known central depression does not have the purpose of guaranteeing complete emptying or removal of the liquid contained in the ampoule by collection of the liquid at the deepest portion of the container. This would only make a sense when an injector needle was provided which extended to the bottom of the ampoule. This however is not the case. The known bottom portion should not be too heavy, so that the ampoule is more easily crushed during its xe2x80x9ctop-headxe2x80x9d emptying.
This function would not be possible in the case of an ampoule made from glass.
Furthermore the known ampoule has a pronounced bottom indentation. It is thus little suited for an in situ lyophilization, since the bottom portion does not guarantee the required surface contact with the cooling plate of the lyophilization device.